JP5057529B2 - Radiation sterilization of medical devices - Google Patents

Description

Detailed Description of the Invention

[Background of the invention]
[Field of the Invention]
The present invention relates to radiation sterilization.

[Description of the latest technology]
The present invention relates to a radially expandable endoprosthesis adapted to be implanted in a body lumen. An “endoprosthesis” corresponds to an artificial device that is placed in the body. “Lumen” means a lumen of a tubular organ such as a blood vessel.

  A stent is an example of such an endoprosthesis. Stents are generally cylindrical devices that function to keep blood vessels or other anatomical lumen areas such as the urinary tract and bile duct clear and sometimes dilated. Stents are often used in the treatment of vascular atherosclerotic stenosis. “Stenosis” means a narrowing or constriction of the diameter of a bodily pathway or opening. In such treatment, the stent strengthens the body's blood vessels and prevents restenosis after angioplasty in the vasculature. By “restenosis” is meant a recurrence of stenosis in a blood vessel or heart valve after being treated (such as by balloon angioplasty, stenting, or valvuloplasty) and apparently successful.

  Treatment of diseased sites or lesions with stents involves both delivery and deployment of the stent. “Delivery” means the introduction and transfer of a stent through a body lumen to an area in a vessel requiring treatment, such as a lesion. “Deployment” corresponds to expanding the intraluminal stent in the treatment area. Stent delivery and deployment places the stent near one end of the catheter, inserts the end of the catheter through the skin and into the body lumen, and advances the catheter in the body lumen to the desired treatment site. This is accomplished by expanding the stent at the treatment site and removing the catheter from the lumen.

  In the case of an expandable balloon stent, the stent is attached near the balloon placed on the catheter. Stent attachment typically involves pressing or crimping the stent onto the balloon. The stent is then expanded by inflating the balloon. The balloon may then be deflated and the catheter may be withdrawn. In the case of a self-expanding stent, the stent may be secured to the catheter via a stretchable sheath or sock. If the stent is in the desired body location, the sheath can be withdrawn, thereby allowing the stent to self-expand.

  The stent must be able to meet a number of mechanical requirements. First, the stent must be able to withstand the structural loads imposed on the stent when supporting the vessel wall, i.e., radial compressive forces. Therefore, the stent must have adequate radial strength. Radial strength is the ability of the stent to withstand radial compressive forces and is due to the strength and stiffness surrounding the circumferential direction of the stent. Thus, radial strength and stiffness may be described as hoop or circumferential strength and stiffness.

  Once expanded, the stent is consistently sized throughout its useful life, despite the various forces that can occur on it, including periodic loads caused by the beating heart. And the shape must be maintained properly. For example, a radially directed force may have a tendency to rewind the stent inward. In general, it is desirable to minimize rewinding.

  In addition, the stent must have sufficient flexibility to handle crimping, expansion, and cyclic loading. Longitudinal flexibility allows the stent to move through tortuous vascular pathways and is suitable for deployment sites that may not be straight or that may be prone to bending Important to make it possible to do. Finally, the stent must be biocompatible so as not to induce any adverse vascular response.

  The structure of a stent is typically composed of a scaffold that includes a pattern or network of interconnecting structural elements, often referred to in the art as struts or bar arms. The scaffold may be formed from a wire, tube, or sheet of material rolled into a cylindrical shape. The scaffold is designed so that the stent can be radially compressed (to allow crimping) and radially expanded (to allow deployment). Conventional stents can expand and contract through the movement of individual structural elements having a pattern relative to each other.

  In addition, medicinal stents can be manufactured by coating the surface of either a metal scaffold or a polymer scaffold with a polymeric carrier comprising an active or biologically active agent or drug. The polymer scaffold can also serve as an active agent or drug carrier.

  After the stent is manufactured, it is typically subjected to sterilization to reduce the stent's bioburden to an acceptable sterility assurance level (SAL). There are many ways to sterilize medical devices such as stents, the most common being treatment with ethylene oxide and treatment with ionizing radiation such as electron beam or gamma radiation. In general, it is desirable that the sterilization procedure has little or no deleterious effect on the material properties of the stent.

[Overview]
Various embodiments of the present invention include a method of sterilizing a stent delivery assembly, the method comprising exposing the stent delivery assembly to radiation from a radiation source, wherein a cover over a selected portion of the assembly is provided. Selectively modifying radiation from a radiation source delivered to a selected portion of the assembly.

  Another embodiment of the invention includes a method of sterilizing a stent delivery assembly, the method comprising exposing a stent delivery assembly encapsulated in a package to radiation from a radiation source, the package comprising the package It includes one or more modifier portions that selectively modify radiation from a radiation source that is delivered to selected portions of the assembly.

  Further embodiments of the invention include a system for sterilizing a stent delivery assembly using radiation, the system comprising a stent delivery assembly and a package having one or more modifier portions, the assembly comprising: Selection of the assembly such that one or more modifier portions disposed within the package modify the radiation delivered to the selected portion of the assembly when radiation is directed from the radiation source to the assembly. Is positioned relative to the marked part.

  Other embodiments of the invention include a system for sterilizing a stent delivery assembly using radiation, the system comprising a stent delivery assembly and a cover covering selected portions of the assembly, the cover comprising Modify the radiation delivered to a selected portion of the assembly when the radiation is directed to the assembly from a radiation source.

  Some other embodiments of the present invention include a method of sterilizing a stent delivery assembly, the method comprising exposing the stent delivery assembly to radiation from a radiation source, the assembly supported by a fixture. And the modifier portion of the fixture selectively modifies the radiation from the radiation source delivered to the selected portion of the assembly.

  Some other embodiments of the present invention include a method of sterilizing a plurality of stent delivery system assemblies using a radiation source, the method including a plurality of stent catheter assemblies in a package supported on a fixture. Placing each assembly in a planar arrangement in the package, exposing the assembly to a radiation beam from a radiation source, the beam comprising a radiation source and a fixture Wherein the package is arranged so that the radiation passes through the plurality of assemblies during the exposure, and the dose delivered is the radiation Depending on the distance between the source and the fixture, one or more assemblies may be delivered at selected portions of the assembly. Rays is arranged in the package to receive the dose.

FIG. 1 shows a stent. FIG. 2 shows a stent delivery assembly. FIG. 3 is a schematic view of a stent delivery assembly disposed in a pouch. FIG. 4A is a schematic illustration of a stent delivery assembly in a pouch placed in a flat box. FIG. 4B is a photograph of a pouch including a stent delivery assembly disposed in a chipboard box. FIG. 5 is a schematic view of a fixture that supports the package. FIG. 6A is a diagram showing the dose delivered into a material against the depth of penetration of radiation for two different density materials. FIG. 6B illustrates an embodiment that modifies radiation exposure to selected portions of the device. FIG. 6C illustrates an embodiment for modifying radiation exposure to selected portions of the device. FIG. 6D illustrates an embodiment for modifying radiation exposure to selected portions of the device. FIG. 7A shows a stent placed over the distal end of the catheter. FIG. 7B shows a sheath placed over the stent. FIG. 7C shows an inner sheath 720 and an outer sheath 725 covering the stent. FIG. 7D shows another embodiment of a cover 730 that is in the form of a semi-cylinder. FIG. 8A is a schematic view of a flexible package having a stent delivery assembly contained therein. FIG. 8B is a side view of the package of FIG. 8A. FIG. 9A is a schematic view of a rigid package with a stent delivery assembly included therein. FIG. 9B is a side view of the package of FIG. 9A. FIG. 10A illustrates a package with a preformed barrier portion having a stent delivery assembly included therein. FIG. 10B is a side view of the package of FIG. 10A. FIG. 11A shows a package including a slot or slot for inserting a barrier element. FIG. 11B is a side view of the package of FIG. 10A. FIG. 12A shows a fixture for supporting a package containing a stent delivery assembly during sterilization. 12B is a side view of the fixture of FIG. 11B supporting a package containing a stent delivery assembly. FIG. 13A is a view showing a fixture including packages arranged in a horizontally stacked arrangement with a slight shift. FIG. 13B is a top view of the fixture in FIG. 13A.

Detailed Description of the Invention
Various embodiments of the invention relate to sterilization of implantable medical devices with radiation. In some embodiments, these devices may be made entirely or partially of a polymer. These embodiments relate to controlling radiation delivered to selected portions of the device.

  The methods and systems described herein can be generally applied to implantable medical devices. These methods and systems are particularly relevant for implantable medical devices having polymer substrates, polymer-based coatings, and / or drug delivery coatings for reasons discussed below. The polymer-based coating may include, for example, an active agent or drug for topical administration to the affected site. An implantable medical device may include a polymeric or non-polymeric substrate with a polymer-based coating.

  Examples of implantable medical devices include self-expandable stents, balloon expandable stents, stent grafts, grafts (eg, aortic grafts), artificial heart valves, cerebrospinal fluid shunts, pacemaker electrodes, and endocardial leads ( For example, Fineline and Endotok available from Abbott Cardiovascular Systems Inc (Santa Clara, Calif.). The basic structure or substrate of the device can be of virtually any design.

  The structure of the stent may in particular comprise a scaffold or substrate comprising a plurality of interconnected structural elements or strut patterns. FIG. 1 shows an example diagram of a stent 100. Stent 100 has a cylindrical shape and includes a pattern with many interconnected structural elements or struts 110. In general, the stent pattern is designed so that the stent can be radially compressed (crimped) and radially expanded (to allow deployment). The pressure involved during compression and expansion is generally distributed throughout the various structural elements of the stent pattern. The present invention is not limited to the stent pattern shown in FIG. The change in stent pattern is virtually unlimited.

  A stent, such as stent 100, can be manufactured from a polymer tube or from a sheet by winding and bonding the sheets to form a tube. A stent pattern can be formed on a polymer tube by laser cutting the pattern on the tube. Representative examples of lasers that can be used include, but are not limited to, excimers, carbon dioxide, and YAG. In other embodiments, chemical etching may be used to form a pattern on the tube.

  Stents have several mechanical requirements that are very important for successful treatment. For example, the stent must have sufficient radial strength to withstand the structural loads imposed on the stent when supporting the vessel wall, ie, radial compressive forces. In addition, the stent must have sufficient flexibility to handle crimping, expansion, and cyclic loading. Bending elements 130, 140, and 150 are subjected to a great deal of pressure and tension, especially during use of the stent.

  It is well known to those skilled in the art that the mechanical properties of a polymer can be modified by applying pressure to the polymer. The strength and modulus of the polymer tends to increase along the direction of the applied pressure. Thus, in some embodiments, the polymer tube can be radially deformed prior to laser cutting to increase radial strength. The increase in strength and modulus can be attributed to circumferentially induced molecular orientation. However, as the temperature of the polymer rises to near or above the glass transition temperature (Tg), some or all of the induced orientation and strength can be lost due to relaxation of the polymer chains. “Glass transition temperature”, or Tg, is the temperature at which an amorphous domain of a polymer changes from a brittle glassy state to a deformable or ductile solid state at atmospheric pressure. In other words, Tg corresponds to the temperature at which the onset of segment motion occurs in the polymer chain. When an amorphous or semi-crystalline polymer is exposed to increasing temperatures, both the expansion coefficient and heat capacity of the polymer increase with increasing temperature, indicating an increase in molecular motion. As the temperature is raised, the actual molecular volume in the sample remains constant, so a higher expansion factor is the increase in free volume associated with the system, and thus the increase in freedom as the molecule moves. Indicates. An increase in heat capacity corresponds to an increase in heat dissipation due to movement. The Tg of a given polymer can depend on the heating rate and can be affected by the thermal history of the polymer. Furthermore, the chemical structure of the polymer greatly affects the glass transition by affecting mobility.

  Sterilization is typically performed on a medical device such as a stent to reduce bioburden on the device. Bioburden generally refers to the number of microorganisms that are contaminating the subject. The degree of sterilization is typically measured by the level of sterility assurance (SAL), which means the probability that there are viable microorganisms on the product unit after sterilization. The SAL required for a product depends on the intended use of the product. For example, products intended for use in the body fluid pathway are considered Class III devices. SALs for various medical devices can be identified in materials from the Association for the Advancement of Medical Instrumentation (AAMI) in Arlington, Virginia.

  Radiation sterilization is well known to those skilled in the art. Various types of medical devices composed entirely or in part of polymers, including but not limited to electron beams (e-beams), gamma rays, ultraviolet rays, infrared rays, ion beams, x-rays, and laser sterilization. Can be sterilized by radiation. The sterilization dose can be determined by selecting a dose that provides the required SAL. One or more passes can be used to expose the sample to the required dose.

  However, it is known that radiation can change the properties of the polymer treated by the radiation. High energy radiation tends to result in ionization and excitation of polymer molecules. These energy-rich species go through a dissociation reaction, a subtraction reaction, and an addition reaction continuously, resulting in chemical stability. The stabilization process can occur during irradiation, immediately after irradiation, or days, weeks, or even months after irradiation, often resulting in physical and chemical cross-linking or strand breaks. The resulting physical changes can include embrittlement, discoloration, odor generation, curing, and softening, among others.

  In particular, the degradation of polymer material and drug performance due to e-beam irradiation sterilization is associated with free radical formation in the device during radiation exposure and reaction with other parts of the polymer chain. The response depends on the e-beam dose and the temperature level.

  Furthermore, exposure to radiation such as e-beams can cause an increase in the temperature of the irradiated polymer sample. The temperature rise is dependent on the exposure level. It has been observed that the stent delivery assembly can rise about 7 ° C. per 12 kGy of radiation exposure. The mechanical properties of the polymer are particularly sensitive to temperature changes. In particular, as the temperature approaches and exceeds the glass transition temperature (Tg), the effect on properties becomes greater. It has been observed that e-beam irradiation of polymer stents can result in strut cracks during deployment due to the occurrence of brittle behavior. Cracks may be due to an increase in temperature as well as a decrease in molecular weight. In addition, temperature increases may result in the loss of some or all of the induced orientation and strength due to relaxation of the polymer chains.

  Furthermore, increasing the temperature can also increase the drug release rate and reduce the drug load on the stent. The drug may also degrade at high temperatures during manufacturing and storage conditions, changing the total drug content and release rate. The dose can be selected to be sufficient to sterilize the stent to the desired extent. As indicated above, the exposure may be one or more passes from the radiation source.

  In general, polymer stents and balloons are more sensitive to radiation exposure than catheters and dispenser coils. Stent and balloon performance is more likely to be adversely affected by the increased temperature and chemical degradation caused by radiation exposure. Therefore, it is important that the radiation exposure delivered to the stent and balloon is within a selected range. The selected range may be, for example, 20-30 KGy, or more strictly 22-27 KGy. On the other hand, the performance of catheters and dispenser coils is less sensitive to radiation exposure. Thus, the catheter and dispenser coil can withstand greater changes in radiation delivered at higher levels. In general, selected portions of a device may have a desired or optimal delivery radiation range that is different from other portions of the device.

  Further, in some embodiments, stents and balloons may require less radiation exposure than catheters and dispenser coils for effective sterilization. Stent processing can result in lower levels of bioburden on the stent as compared to the catheter. For example, the stent may be exposed to a solvent such as isopropyl alcohol or acetone during processing. Further, the stent material may be exposed to high temperatures during various processing steps. Thus, a stent may have a bioburden of less than 5 cfu, or even as low as 0 to 1 cfu. “CFU” is an indicator of bioburden and is an abbreviation of “colony forming unit” which is an indicator of the number of viable bacteria. For 1.5 cfu products the required or final sterilization dose is 15 KGy and for 8 cfu products the radiation dose is 17.5 KGy. The delivery system may require a substantially higher dose than other parts of the assembly.

  Accordingly, it may be desirable to selectively modify the radiation delivered to a selected portion of an implantable medical device, such as a stent delivery assembly, for a given dose of radiation from a radiation source. For example, the dose delivered to the stent may be reduced. This should reduce performance degradation due to radiation. Alternatively, it may be desirable to increase the dose delivered to a selected portion of the instrument. Some parts of the device may require higher doses due to the high bioburden. Also, some parts may receive less delivery dose than needed due to shielding of radiation by the package or other parts of the device.

  Stents are typically sterilized, packaged, stored, and transported in a “ready to implant” configuration, where the stent is placed at the end of a delivery system that includes a catheter and a dispenser coil. Has been. FIG. 2 shows the stent delivery assembly 200 with the stent 205 positioned at the distal end of the delivery system 215. The stent 205 may be crimped onto the balloon. A sheath may also be placed on the stent to secure the secure to the balloon. The stent delivery assembly 200 can be packaged before or after radiation sterilization.

  Stents and stent delivery assemblies are typically stored, transported, and sterilized in a sealed storage container. Such containers are adapted to protect the assembly from damage and environmental exposure (humidity, oxygen, light, etc.) that may have an adverse effect on the stent. The storage container for the stent and delivery system may be designed to be any convenient form or shape that allows for the effective encapsulation of the stent and delivery system assembly contained therein. However, the container may be small and shaped to minimize the storage space occupied by the container. The container that is primarily intended to protect the stent and delivery system from environmental exposure may be a pouch or sleeve. FIG. 3 shows a schematic view of the stent delivery assembly 200 disposed in the pouch 230. As can be seen from FIG. 3, the assembly 200 is arranged or stored in a planar configuration.

  In one commercially useful embodiment, the pouch may have a rectangular piece that is 8 inches to 12 inches wide and 10 inches to 13 inches long. Also, depending on the type of material used to construct the pouch, the container may be of varying degrees of rigidity or flexibility. The container may be made of a flexible film rather than a hard material. This is because the flexible film is less likely to be weakened by changes in atmospheric conditions during storage. For example, the container may be composed of two sheets or thin layers bonded along the edge. Also, the container is composed of a single sheet or thin layer that is folded and sealed at all edges, or sealed at all unfolded edges, or It may consist of a bag or pocket that is sealed on one or more edges. The pouch may be made of a polymer, glass, ceramic, metallic material, or a combination thereof. Typically, the pouch is made of metal foil.

  The pouch containing the stent and delivery system may further be placed in a rigid container to protect the pouch contained therein and the stent and delivery system. The hard container may be a box such as a chipboard box. FIG. 4A shows a schematic diagram of a stent and delivery system 200 in a pouch 230 in a flat chipboard box 240. FIG. 4B shows a photograph of the pouch 250 including the stent and delivery system placed in the chipboard box 255.

  A system for sterilizing a packaged stent delivery assembly includes a radiation source, such as an e-beam source, and a fixture for supporting the package. The support fixture moves past the e-beam source on the conveyor arrangement, for example, in a manner that the e-beam is directed onto the stent delivery assembly. FIG. 5 shows a schematic view of a fixture 500 that supports a package 505 that includes a stent delivery assembly (not shown). The fixture 500 includes a bottom support 525 and a back support arm 530. Radiation source 535 directs radiation as indicated by arrow 540. The fixture 500 can be moved past the radiation source 535 by a conveyor system (not shown) as indicated by arrow 545 to sterilize the stent delivery assembly in the package 505.

  In some embodiments, as indicated by E-beam pulse 542, the cross-sectional shape of the E-beam is circular or generally circular. In such an embodiment, the E-beam is pulsed up and down to illuminate the package 505 and stent delivery assembly along the axis from position X to position Y, as indicated by arrow 543. Thus, the entire selected portion of the package 505 and the stent delivery assembly can be illuminated as the fixture 500 is carried in the direction indicated by arrow 545. In such an embodiment, the beam can be pulsed up and down, for example, 64 times per second.

  As indicated above, as shown in FIG. 5, more or less radiation may be delivered by the radiation source to selected portions of the implantable medical device. In some embodiments of the invention, a cover covering selected portions of an implantable medical device, such as a stent delivery assembly, selectively modifies radiation from a radiation source that is delivered to selected portions of the assembly. To do. In one embodiment, the radiation can be modified by the cover so that the radiation delivered to the selected portion is within an optimal delivery radiation range. The cover selectively directs radiation from the radiation source so that the radiation delivered to the selected portion of the assembly is at a higher or lower level than the radiation delivered to the selected portion in the absence of the cover. Can be corrected.

  In other embodiments, the implantable medical device may be encapsulated in a package that includes one or more modifier portions. The modifier portion can selectively modify the radiation from the radiation source that is delivered to the selected portion of the assembly. In one embodiment, the radiation can be modified by the modifier portion so that the radiation delivered to the selected portion is within the optimal delivery radiation range. The modifier portion is removed from the radiation source so that the radiation delivered to the selected portion of the assembly is at a higher or lower level than the radiation delivered to the selected portion when there is no modifier portion. Can be selectively modified.

  As indicated above, a radiation barrier, such as a cover or modifier portion, can increase or decrease the radiation delivered to the selected portion. The radiation barrier can cause such an increase / decrease by absorption, reflection (or backscattering), or a combination thereof. The radiation modification mode depends on factors such as the material thickness, density, and reflective properties of the cover or modifier portion.

  In general, the dose delivered into a material that absorbs radiation varies depending on both the depth of penetration (thickness) and the density of the material. FIG. 6A is curves C1 and C2 showing the dose delivered into the material that absorbs radiation versus the depth of penetration of the radiation for two different density materials.

  FIG. 6A shows that the radiation barrier element can increase or decrease the delivered radiation or dose above or below the initial radiation Di depending on its thickness. FIG. 6A shows dose versus density (or depth) through which electrons have passed. Di is the radiation that the selected portion will receive if there is no barrier between the selected portion and the radiation source, and no backscatter from the material on the side opposite the selected portion from the radiation source. It can be a dose. FIG. 6A also shows that as the density of radiation barrier elements increases, the range of increasing radiation increases to a greater thickness. Both the density and thickness of the barrier element material can be selected to obtain selected radiation that is delivered to the selected portion. In order for all devices to receive an equal dose at a selected portion (eg, all stents have the same dose), when multiple devices are sterilized sequentially or simultaneously, the electrons hit the selected portion By the time, it must pass through an equal density. Various materials that absorb or modify radiation are known to those skilled in the art, including various types and forms of polymers such as foam. “Foam” may mean a polymer foam, for example, a polystyrene foam such as Styrofoam from Dow Chemical Company (Midland, MI).

  A radiation barrier can modify or reduce radiation by reflecting or backscattering the radiation. In addition to radiation barriers such as package covers and modifier portions, radiation from the radiation source may be backscattered into the device, eg, from a portion of the supporting fixture back (eg, support arm 530 in FIG. 5). Also good. Metals generally have a tendency to reflect various types of radiation, such as electromagnetic radiation, electron beam, and ion beam radiation. Exemplary metals that can be used as the reflective barrier material include aluminum and stainless steel.

  Packages, fixtures, barriers, etc. can be designed so that the radiation does not pass through a density sufficient to reduce the dose to selected parts to zero. Furthermore, the packages, fixtures, barriers, etc. can be designed such that selected parts receive a minimum dose Dm, eg 25 kGy. The curve C1 rises from Di to Dp, then falls to Dm, and finally falls to zero. Therefore, the dose variation is large.

  Embodiments of the present invention include selective radiation modification to obtain a selected delivered radiation dose at a selected portion of the device. As described below, selective radiation correction can be performed using a cover, a modifier portion in the package, a fixture, or a combination thereof. Three sets of selective modification embodiments are described herein.

  In a first set of embodiments, the radiation can be selectively modified using a barrier between the radiation source and the selected portion. The barrier is in front of the selected portion so that the radiation from the radiation source passes through the barrier to the selected portion. In such embodiments, the barrier thickness, material density, or both can be selected to obtain a selected radiation dose to a selected portion.

  In a second set of embodiments, the barrier behind or on the side of the selected portion opposite the incoming radiation selectively modifies the radiation. In one such embodiment, the radiation can be selectively modified using a barrier made of a reflective material that backscatters or reflects the radiation back to selected portions. The radiation passes through the selected portion to reach the barrier, which reflects a portion of the radiation back to the selected portion. The total dose delivered to the selected portion is the sum of the radiation that first passes through the selected portion and the reflected radiation.

  In an alternative embodiment of the second set of embodiments, the barrier is made from a non-reflective material. The barrier may act, for example, as a barrier that reduces backscattered radiation from a portion of the fixture or prevents this backscattered radiation from increasing the radiation delivered to the selected portion. it can.

  In a third set of embodiments, radiation can be selectively modified using barriers on the front and back of selected portions. The radiation passes through the front barrier to reach the selected portion and is then backscattered to the selected portion by the back barrier. The total dose delivered to the selected part is the sum of the radiation modified by the initial barrier and the radiation reflected from the back barrier to the selected part. In such an embodiment, the properties of the front barrier (thickness, density) and the reflective properties of the back barrier can be selected to obtain a selected delivered radiation dose to a selected portion.

  6B-6D show embodiments of a first set, a second set, and a third set, respectively. 6B-6D show an enlarged view of a cross section of a selected portion 605 of an implantable medical device, with radiation Di being directed at the device, as indicated by arrow 610.

  FIG. 6B showing a first set of embodiments shows an arrangement 601 with a radiation barrier 625. In FIG. 6B, the radiation barrier 625 may correspond to a portion of the package cover or modifier portion on the side of the selected portion 605 facing the dose Di incident radiation 610. The radiation 610 can be modified to have a dose D 1 that is radiation delivered to the selected portion 605 by the barrier 625.

  In FIG. 6B, the radiation delivered to the selected portion can be increased more than Di or decreased less than Di. The barrier 625 may be a material having the dose curve C1 of FIG. 6A. As shown in FIG. 6A, when the thickness of the barrier 605 is thinner than Ti, D1 can be increased to be larger than Di. If the thickness is greater than Ti, D1 can be reduced until it is less than Di. To obtain a selected delivery dose with a thinner barrier, a denser material can be used. D1 increases to 44 kGy. For example, the thickness can be changed so that D1 decreases to 30 kGy. An exemplary embodiment of the barrier material may be a metal.

  FIG. 6C showing a second set of embodiments shows an arrangement 602 with a radiation barrier 630 behind a selected portion 605. The radiation delivered to the selected portion can be increased to be greater than Di. The radiation barrier 630 may correspond to a side cover, modifier portion, or part of a fixture of the selected portion 605. Even when the barrier 630 is a non-reflective material, an increase in radiation delivered to the selected portion 605 due to reflection of radiation from the opposite side of the selected portion 605 is reduced or prevented. If the barrier 630 is a reflective material, D2 that is part of the radiation 610 is reflected toward the selected portion 605. The total amount of radiation delivered is the sum of Di and D2.

  In an exemplary embodiment, Di is 25 kGy so that the initial exposure dose is 25 kGy. D2 that is part of the 25 kGy radiation is reflected by the barrier 630 and is, for example, 5 kGy. The total amount of radiation delivered is the sum of Di and D2, ie 30 kGy.

  FIG. 6D showing a third set of embodiments shows a barrier 615 in front of the selected portion 605 and a radiation barrier 620 behind the selected portion 605. The barrier 615 can modify the radiation 610 so that the dose is D1. D1 can be higher or lower than Di depending on the thickness and density of the barrier 615.

If the barrier 620 is a reflective material, D2 that is part of the radiation 610 is reflected in a direction back to the selected portion 605. The total amount of radiation delivered is the sum of D1 and D2. If the barrier 620 is a reflective material, there are at least three possibilities:
(1) If the barrier 615 has a thickness and density such that D1 is greater than Di and D2 further increases the total amount to be greater than Di, the total amount of radiation delivered will exceed Di.
(2) If D1 is less than Di and the barrier 615 has a thickness and density that increases D2 so that the total amount is greater than Di, then the total amount of radiation delivered will exceed Di.
(3) If the barrier 615 has a thickness and density such that D1 is less than Di and the sum of D1 and D2 is less than Di, the total amount of radiation delivered to the selected portion 605 is less than Di .

  If the barrier 620 is a non-reflective material, the total amount of radiation delivered can be greater than or less than Di depending on the thickness and density of the barrier 615.

  In the exemplary embodiment, barrier 620 is a reflective material, Di is 40, D1 is 44 kGy, and D2 is 6 kGy. The total dose delivered is 50 kGy.

  In some embodiments, the cover may include a sheath or sleeve disposed around a selected portion of the stent delivery assembly. In such an embodiment, the selected portion may include a stent with a sheath or sleeve disposed along the outer periphery of the stent. Further, the selected portion may be a strip of polymer material that is folded to enclose the selected portion of the assembly and clipped to secure the folded strip.

  In some embodiments, the cover for the selected portion includes a first side and a second side. The first side covers the side of the selected portion facing the incoming radiation, and the second side covers the side of the selected portion opposite the incoming radiation. The first aspect can modify radiation by absorption. The second aspect can modify the radiation by backscattering the radiation toward the selected portion. Alternatively, the cover is constructed from a non-reflective material so that there is little modification due to backscatter. In another embodiment, the cover covers the side of the selected portion facing the incident radiation and there is no cover on the side of the selected portion opposite the incident radiation.

  FIG. 7A shows a stent 705 positioned over the distal end 700 of the catheter. FIG. 7B shows a sheath 710 positioned over the stent 705. The end of the sheath 710 can also be closed to reduce or prevent exposure of the stent to bioburden. The sheath 710 may serve the dual purpose of securing the stent to the catheter and providing a radiation barrier. Radiation can be directed to the distal end 700 as indicated by arrow 715. The side 720 of the sheath 710 can be adapted as described above to increase or decrease the radiation delivered to the stent 705. Similarly, the side 725 can be adapted to increase the dose delivered to the stent 705 by reflection of the radiation. The thickness of the sheath 710 is Ts and can be adjusted to modify the radiation directed at the stent to the desired extent. The Ts may be such that the stent receives delivery radiation that is within the desired or optimal range.

  In addition, a material having a density that achieves the desired degree of modification can be selected. Thickness, density, and material can be selected so that the radiation delivered to the stent increases or decreases to a selected range. In another embodiment, a sheath 710 can be placed over a portion of the catheter to modify the radiation delivered to that portion.

  FIG. 7C shows an alternative embodiment of the barrier, showing an inner sheath 720 and an outer sheath 725. Inner sheath 720 and outer sheath 725 can work together to modify the radiation delivered to the stent. Inner sheath 720 may typically be the sheath used to secure the stent to the catheter, while outer sheath 725 may be designed to condition the radiation delivered to the stent. . For example, the thickness Tso of the outer sheath 725 can be adjusted, and the density of the sheath material can be selected to achieve the desired modification of the radiation. Various combinations of materials and thicknesses of inner sheath 720 and outer sheath 725 can be used to provide optimal delivery radiation to the stent.

  FIG. 7D shows another embodiment of a cover 730 that is in the form of a semi-cylinder. Cover 730 covers the sides of selected portion 706 of distal end 700 of catheter 700. The cover 730 may be a reflective material such as metal.

  The aspect of the modifier portion of the package can selectively modify the radiation from the radiation source such that the radiation delivered to the selected portion of the stent delivery assembly, eg, the stent, is within a selected range. it can. In some embodiments, the modifier portion may have different radiation absorption and reflection properties than other portions of the package. In such embodiments, the modifier portions may have different thicknesses, densities, or may be made of different materials. In one embodiment, the modifier portion may be coupled or attached to a package having an otherwise uniform or substantially uniform thickness, material, and density. For example, the modifier portion may be a piece of metal, foam, plastic, or other material taped, glued, stapled, or attached to the package. In the exemplary embodiment, the modifier portion may be included in, on, or integral with the pouch 200 shown in FIG. 3 or the box 240 shown in FIG. 4A.

  In some embodiments, the package may have a modifier portion that is located on the side of the selected portion facing the incident radiation. In that case, the modifier part can modify the radiation by absorption. Additionally or alternatively, the package may have a modifier portion located on the side of the selected portion opposite the incoming radiation. Such a modifier portion can modify the radiation by reflection or backscattering of the radiation towards the selected portion. The thickness and density of the modifier portion can be selected to obtain selected radiation delivered to the selected portion.

  FIG. 8A shows a schematic view of a flexible package 800 with a stent delivery assembly 805 included therein. Barrier element 810 is attached to a portion of package 800. The stent 815 of the assembly 805 is located behind the barrier element 810. FIG. 8B shows a side view of the package 800 and shows the barrier element 810. FIG. 8B shows that the package 800 may optionally have a barrier element 820 on the opposite side. In the exemplary embodiment, barrier element 810 can selectively modify radiation directed at assembly 800 from a radiation source, as indicated by arrow 825. In addition, the barrier element 820 can also modify backscattered radiation, as indicated by arrow 830, which is reflected, for example, by a supporting fixture (not shown). Barrier element 830 may be a reflective material that increases the radiation delivered to selected portions by reflection of the radiation passing through barrier 810. In an alternative embodiment, the package 800 may have a barrier element 820 and may not have a barrier element 810.

  Barrier elements 810 and 820 may be the same or different thickness, density, or material. Further, the package 800 may optionally include barrier elements 835, 845, or both to modify the radiation delivered to a portion of the catheter or dispenser coil. As discussed with respect to FIGS. 6B-6D, the thickness, density, or material of the barrier elements 810, 820, 835, and 845 may be selected or adjusted to provide the desired or optimal delivery to the stent 815 and selected portion 840. Radiation exposure can be obtained. In an alternative embodiment, the barrier element may be attached to the inner surface of the package 800.

  9A-9B show a schematic view of a rigid package or box 900 in which the stent delivery assembly 905 is contained, eg, the box 230 shown in FIG. Radiation is directed to the package 900 as indicated by arrow 925. The backscattered radiation indicated by arrow 930 can arrive from the fixture, for example. As shown, the assembly 905 is encapsulated within a flexible package or pouch 903 that is contained within the package 900.

  FIG. 9A shows a front view of the package 900 with barrier elements 910 and 935 attached to the package 900. The barrier element 910 is in front of the stent 915 and the barrier element 935 is in front of the portion 940 of the catheter 905. FIG. 9B shows a side view of the package 900. FIG. 9B shows that the package 900 optionally includes barrier elements 920, 945, or both on the opposite side of the package 900. In alternative embodiments, the package 900 may have either or both of the barrier elements 920 or 945 and may not have the barrier elements 910 and 935. As discussed with respect to FIGS. 6B-6D, the thickness, density, or material of the barrier elements 910, 920, 935, and 945 may be selected or adjusted to provide the desired or optimal delivery radiation exposure to the stent 915 and portion 940. Obtainable.

  In another embodiment, the modifier portion of the package may be integrated with or incorporated into the package. FIG. 10A shows a package 1000 with a stent delivery assembly (not shown) contained therein. Package 1000 includes a barrier portion 1005 that is integral with, pre-formed, or incorporated with package 1000. FIG. 10B shows a side view of the package 1000 and shows the stent delivery assembly 1015 included within the package 1000. The package 1000 may have a barrier portion 1010 in some cases. In an alternative embodiment, the package 1000 may have a barrier element 1010 and may not have a barrier element 1005. The stent 1020 is located between the barrier portion 1005 and the barrier portion 1010, and the barrier portion 1010 may also be integrated with the package 1000, pre-formed, or incorporated. Package 1000 may be formed of a plastic material and barrier portions 1005 and 1010 may be pre-formed as part of package 1000.

  In further embodiments, the package may have a receptacle or sleeve that allows insertion of the barrier element. The inserted barrier element can selectively modify the radiation delivered to selected portions of the stent delivery assembly. FIG. 11A shows a package 1100 with a stent delivery assembly (not shown) contained therein. Package 1100 includes a slot or slot 1105 that is integral with or attached to package 1100. The outlet 1105 has an opening 1110 that allows the insertion of a barrier element 1115 as indicated by arrow 1120. FIG. 11B shows a side view of the package 1100 and shows the stent delivery assembly 1125 included within the package 1100. Package 1100 may also have a slot 1135 for barrier element 1140, as indicated by arrow 1145. In an alternative embodiment, the package 1100 may have an inlet 1135 with a barrier element 1140 and may not have an inlet 1105 with a barrier element 1115. The stent 1130 is located between the insertion port 1105 and the insertion port 1135, which may also be integrated with or attached to the package 1100.

  Another embodiment of the present invention may include sterilizing an implantable medical device with a fixture that selectively modifies the radiation delivered to a selected portion of the assembly. In such embodiments, the fixture may be a support arm that is opposite the device facing the directed radiation. In certain embodiments, the support may include a modifier portion that selectively reflects or backscatters radiation to selected portions. For example, the modifier portion may be composed of a material that is more reflective than the other portions of the support arm. In another embodiment, the modifier portion may selectively absorb radiation or may have lower reflective properties than other portions of the support arm.

  FIG. 12A shows a fixture 1200 for supporting a package containing a stent delivery assembly during sterilization. The fixture 1200 includes a bottom support 1205 and a back support 1210. The back support 1210 has a modifier element 1215. The modifier element 1215 has radiation absorption / reflection properties that are different from other parts of the fixture.

  FIG. 12B shows a side view of a fixture 1200 that supports a package 1220 that includes a stent delivery assembly 1255. Radiation is directed at the package 1220 as indicated by arrow 1235. Stent 1230 is located between modifier element 1215 and directed radiation 1235. When the back support 1215 is constructed from a reflective material, the non-reflective modifier element 1215 reduces or eliminates backscatter from the back support 1210 to the stent 1230 to reduce the radiation delivered to the stent 1230. Can be reduced. For example, the back support 1215 may be composed of aluminum and the modifier element 1215 may be a non-reflective material such as a foam.

  Another embodiment of the invention may include sterilizing a plurality of stent delivery assemblies disposed on the fixture. A plurality of packages containing the assembly may be placed on the fixture. The assemblies may be arranged in a planar arrangement, such as in box 240 of FIG. 4A. The e-beam from the e-beam source may be acute with respect to the planar arrangement of the package located between the radiation source and the fixture. These packages are arranged in a horizontally stacked arrangement so that radiation passes through multiple assemblies during exposure. As a result, the dose delivered to the assembly varies depending on the distance between the radiation source and the fixture. In such embodiments, one or more assemblies may be placed in a package such that selected portions of the assembly receive a selected delivered radiation dose.

  FIG. 13A shows a fixture 1300 that includes packages 1305 arranged in a horizontally stacked arrangement with a slight offset. Although only three packages are shown, it should be understood that the method described applies to more than three. The number of packages is limited by the size of the fixture. The fixture 1300 includes a bottom support 1302 and a back support 1304. Each package 1305 includes a stent delivery assembly 1310 with a stent 1315 disposed at the distal end of the catheter. FIG. 13B shows a top view of fixture 1300 and package 1305 along line AA. The radiation source directs the radiation beam as indicated by arrow 1320. Radiation beam 1320 is at an acute angle of angle θ with respect to the front of package 1305. The radiation delivered to the assembly 1310 in each package 1305 decreases with distance along a line parallel to the front of the package 1305, as indicated by arrow 1335. Selected portions of assembly 1310, such as stent 1315, may be placed within one or more packages 1305 such that the selected portion has selected delivery radiation. The radiation delivered to the assembly 1310 or selected portion can be increased by appropriate selection of the material of the back support 1304. If the back support 1304 is constructed from a reflective material, the radiation delivered to the assembly 1310 or selected portions can be increased. Alternatively, if the back support 1304 is constructed from a non-reflective material such as a foam, the increase in delivery radiation due to the reflected radiation can be reduced or prevented. Further, a modifier portion 1215 as shown in FIGS. 12A-12B can be used with the fixture 1300 to selectively modify the radiation delivered to the selected portion.

  The basic structure or substrate of the stent may be fully or at least partially biodegradable polymer or combination of biodegradable polymers, biologically stable polymer or biologically stable polymer combination, or It may be made from a combination of a biodegradable polymer and a biologically stable polymer. In addition, polymer-based coatings for device surfaces can be biodegradable polymers or combinations of biodegradable polymers, biostable polymers or combinations of biostable polymers, or biodegradable polymers and biologicals. A combination of chemically stable polymers may be used.

  Polymers for use in making implantable medical devices such as stents may be biologically stable, bioabsorbable, biodegradable, or biologically erodible. Biologically stable means a polymer that is not biodegradable. The terms biodegradable, bioabsorbable, and biologically erodible are used interchangeably and can be completely degraded and / or eroded when exposed to bodily fluids such as blood, and A polymer that can be gradually resorbed, absorbed and / or eliminated by the body. The process of polymer degradation and absorption can be caused, for example, by hydrolysis and metabolic processes.

  After the process of degradation, erosion, absorption, and / or resorption is complete, if the coating is applied on a biologically stable scaffold that does not remain part of the stent, the polymer will remain on the device. It will be understood that nothing remains. In some embodiments, negligible traces or residues may be left behind. In the case of stents made of biodegradable polymers, the stent is intended to remain in the body for a period of time until the intended function of, for example, maintaining vascular patency and / or drug delivery is achieved. Yes.

  Representative examples of polymers that can be used to produce implantable medical device substrates or coatings for implantable medical devices include, but are not limited to, poly (N-acetylglucosamine) (chitin) , Chitosan, poly (hydroxyvalerate), poly (lactide-co-glycolide), poly (hydroxybutyrate), poly (hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly (glycolic acid) , Poly (glycolide), poly (L-lactic acid), poly (L-lactide), poly (D, L-lactic acid), poly (L-lactide-co-glycolide), poly (D, L-lactide), poly (Caprolactone), poly (trimethylene carbonate), polyethylene amide, polyethylene acrylate, poly (Glycolic acid-co-trimethylene carbonate), co-poly (ether-ester) (for example, PEO / PLA), polyphosphazene, biomolecules (such as fibrin, fibrinogen, cellulose, starch, collagen, and hyaluronic acid), polyurethane , Silicones, polyesters, polyolefins, polyisobutylene and ethylene-alpha olefin copolymers, copolymers other than acrylic polymers and polyacrylates, vinyl halide polymers and copolymers (polyvinyl chloride, etc.), polyvinyl ether (polyvinyl methyl ether) Etc.), poly (vinylidene chloride) (polyvinylidene chloride, etc.), polyacrylonitrile, polyvinyl ketone, polyvinyl aromatic (polystyrene, etc.), polyvinyl ester (polyvinyl acetate, etc.) ), Acrylonitrile-styrene copolymer, ABS resin, polyamide (such as nylon 66 and polycaprolactam), polycarbonate, polyoxymethylene, polyimide, polyether, polyurethane, rayon, rayon triacetate, cellulose, cellulose acetate, cellulose butyrate, butyric acetate Examples include cellulose, cellophane, cellulose nitrate, cellulose propionate, cellulose ether, and carboxymethylcellulose.

  Other representative examples of polymers that may be particularly suitable for use in manufacturing implantable medical devices according to the methods disclosed herein include ethylene vinyl alcohol copolymers (generally the generic name EVOH Or known by the trade name EVAL), poly (butyl methacrylate), poly (vinylidene fluoride-co-hexafluoropropene) (e.g., available from SOLEF 21508, Solvay Solexis PVDF (Trosphere, NJ)) , Polyvinylidene fluoride (otherwise known as KYNAR, available from ATOFINA Chemicals, Philadelphia, Pennsylvania), ethylene-vinyl acetate copolymers, and polyethylene Glycol.

  The non-polymeric substrate of the device may be made from a metallic material or alloy, and the alloy may be, for example, but not limited to, cobalt chromium alloy (ELGILOY), stainless steel (316L), high nitrogen stainless steel (eg, BIODUR). 108), cobalt chromium alloy L-605, "MP35N", "MP20N", ELASTINITE (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof. “MP35N” and “MP20N” are registered in Standard Press Steel Co. (Jenkintown, Pennsylvania) is a trade name for alloys of cobalt, nickel, chromium and molybdenum. “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum.

Drugs or active substances can include, but are not limited to, any substance that can exert a therapeutic, prophylactic, or diagnostic effect. Drugs for use in implantable medical devices such as stents and unload-loaded scaffold structures may be any therapeutic, prophylactic, or diagnostic agent, or combinations thereof. Examples of active substances include anti-activities such as actinomycin D, or derivatives and analogs thereof (COSMEGEN manufactured by Sigma-Aldrich (1001 West Saint Paul Avenue, Milwaukee, WI53233) or available from Merck). Examples include proliferative substances. Synonyms for actinomycin D include dactinomycin, actinomycin IV, actinomycin I ₁ , actinomycin X ₁ , and actinomycin C ₁ . Bioactive agents are also anti-tumor substances, anti-inflammatory substances, antiplatelet substances, anticoagulants, antifibrin substances, antithrombin substances, antimitotic substances, antibiotics, antiallergic substances, and antioxidants. It can be classified as a genus of substances. Examples of such anti-tumor substances and / or anti-mitotic substances include paclitaxel (for example, TAXOL® from Bristol-Myers Squibb Co. (Stanford, Conn.)), Docetaxel (for example, Aventis Taxotere (registered trademark) manufactured by SA (Frankfurt, Germany), methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (eg, Pharmacia & Upjohn, Peapack, NJ), Adriamycin (registered trademark) And mitomycin (eg, Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.) And the like.

  Examples of such antiplatelet substances, anticoagulants, antifibrin substances, and antithrombin substances include aspirin, heparin sodium, low molecular weight heparin, heparinoid, hirudin, argatroban, forskolin, bapiprost, prostacyclin, and prostacyclin. Analogs, dextran, D-phe-pro-arg-chloromethyl ketone (synthetic antithrombin), dipyridamole, glycoprotein IIb / IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and Angiomax a (Biogen, Inc. ( Thrombin inhibitors such as Cambridge, Massachusetts)). Examples of such cytostatic or antiproliferative substances include Angiopeptin, Captopril (for example, Capoten (registered trademark) and Capozide (registered trademark) manufactured by Bristol-Myers Squibb Co. (Stanford, Conn.)). ), Cilazapril or lisinopril (eg, Privilil (registered trademark) and Prinzide (registered trademark) manufactured by Merck & Co., Inc. (White House Station, NJ)), calcium channel blockers (nifedipine, etc.) ), Colchicine, protein, peptide, fibroblast growth factor (FGF) antagonist, fish oil (ω3-fatty acid), histamine antagonist, lovastatin (HMG-CoA reversion) Enzyme inhibitors, cholesterol-lowering drugs, trade name Mevacor (trademark) manufactured by Merck & Co., Inc. (White House Station, NJ), monoclonal antibody (specific to platelet-derived growth factor (PDGF) receptor) Etc.), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidines (PDGF antagonists), and nitric oxide. An example of an antiallergic substance is permirolast potassium. Other therapeutic or therapeutic agents that may be suitable agents include cisplatin, insulin sensitizers, receptor tyrosine kinase inhibitors, carboplatin, α-interferon, genetically modified epithelial cells, steroidal anti-inflammatory Substance, non-steroidal anti-inflammatory substance, antiviral drug, anticancer drug, anticoagulant, free radical scavenger, estradiol, antibiotic, nitric oxide donor, superoxide dismutase, superoxide dismutase mimic, 4-amino- 2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, ABT-578, clobetasol, cytostatic substance, its prodrug, its covalent drug (co-drug) ), And combinations thereof That. Other therapeutic agents or therapeutic agents include rapamycin and structural derivatives or functional analogs thereof such as 40-O- (2-hydroxy) ethyl-rapamycin (known under the trade name EVEROLIMUS), 40-O- Mention may be made of (3-hydroxy) propyl-rapamycin, 40-O- [2- (2-hydroxy) ethoxy] ethyl-rapamycin, methyl rapamycin, and 40-O-tetrazole-rapamycin.

  Stent storage containers, such as package 230 in FIG. 3 or package 1100 in FIGS. 11A-11B, may be made of a variety of materials that form a barrier when sealed. For example, the stent storage container may be made of a polymer, glass, ceramic, or a metallic material such as aluminum, stainless steel, or gold. If made of a metallic material, the container may be formed of a metallic film, for example. Suitable examples of films include, but are not limited to, gold, platinum, platinum / iridium alloys, tantalum, palladium, chromium, and aluminum. Suitable materials for the container can also include oxides of the aforementioned metals, such as aluminum oxide. Pharmaceutical storage containers can be obtained, for example, from Oliver Products Company (Grand Rapids, Michigan).

  Suitable polymers for constructing a stent storage container include polyolefins, polyurethanes, cellulosic materials (ie, polymers having monomer units derived from cellulose), polyesters, polyamides, poly (hexamethylene isophthalamide / terephthalamide). (Commercially available as Selar PA ™), poly (ethylene terephthalate-co-p-oxybenzoate) (PET / PHB, for example, a copolymer having about 60-80 mole percent PHB), poly ( Hydroxyamide ether), polyacrylates, polyacrylonitrile, acrylonitrile / styrene copolymers (commercially available as Lopac ™), rubber-modified acrylonitrile / acrylate copolymers (commercially available as Barex ™) Liquid crystal polymer (LCP) (eg, Vectra ™ available from Hoescht-Celanese, Zenite ™ available from DuPont, and Xydar ™ available from Amoco Performance Chemicals, poly (phenylene sulfide), Polystyrene, polypropylene, polycarbonate, epoxy composed of diepoxide based on bisphenol A using amine vulcanization, aliphatic polyketone (eg, Carylon ™ available from Shell and Ketonex ™ available from British Petroleum) , Polysulfone, poly (ester sulfone), poly (urethane-sulfone), poly (carbonate-sulfone), poly (3-hydroxyoxe) Tan), poly (amino ether), gelatin, amylose, parylene-C, parylene-D, and parylene-N.

Exemplary polyolefins include those based on alpha monoolefin monomers having about 2 to 6 carbon atoms and halogen substituted olefins, ie halogenated polyolefins. Examples include, but are not limited to, low to high density polyethylene, essentially unplasticized poly (vinyl chloride), poly (vinylidene chloride) (Saran ™), poly (vinyl fluoride), poly (Vinylidene fluoride), poly (tetrafluoroethylene) (Teflon), poly (chlorotrifluoroethylene) (Kel-F ™), and mixtures thereof are suitable. Low density to high density polyethylene is generally understood to have a density of about 0.92 g / cm ³ to about 0.96 g / cm ³ , but a clear line for classifying the density may be drawn. Not possible, the density can vary from supplier to supplier.

  Exemplary polyurethanes have a glass transition temperature higher than the storage temperature or ambient temperature, for example, have a glass transition temperature of at least 40 ° C. to 60 ° C., or hydrocarbons, silicones, fluorosilicones, or mixtures thereof Polyurethane having a nonpolar soft part containing For example, Elast-Eon ™ from Elastomedic / CSIRO Molecular Science is a non-polar soft part made of 1,4-butanediol, 4,4′-methylenediphenyl diisocyanate, as well as poly (hexamethylene oxide) Polyurethane having a soft part composed of a mixture of (PHMO) and bishydroxyethoxypropyl polydimethylsiloxane (PDMS). A useful example has a mixture of 20 wt% PHMO and 80 wt% PDMS.

  Representative examples of cellulosic materials include, but are not limited to, cellulose acetate, ethyl cellulose, cellulose nitrate, cellulose acetate butyrate having a degree of substitution (DS) greater than about 0.8 or less than about 0.6. , Methylcellulose, and mixtures thereof.

  Representative polyesters include, but are not limited to, saturated or unsaturated polyesters such as poly (butylene terephthalate), poly (ethylene 2,6-naphthalenedicarboxylate) (PEN), and poly (ethylene terephthalate). It is done.

  Representative polyamides include, but are not limited to, nylon-6, nylon-6,6, nylon-6,9, nylon-6,10, nylon-11, aromatic nylon MXD6 (Mitsubishi Gas Chemical America, Inc. And the like, and mixtures thereof, crystalline or amorphous polyamides.

  Exemplary polyacrylates include, but are not limited to, poly (methyl methacrylate) and polymethacrylate.

  The stent storage container may also be composed of copolymers of vinyl monomers and olefins such as poly (ethyl vinyl acetate).

While particular embodiments of the present invention have been shown and described, it will be apparent to those skilled in the art that changes and modifications can be made in a wider variety of aspects without departing from the invention.

Claims (25)

The radiation from the radiation source comprises exposing the stent delivery assembly, a cover for covering a selected portion of the assembly, selectively modifies the radiation from the radiation source to be delivered to a selected portion of said assembly ,
A selected portion of the assembly has an optimal delivery radiation range that is different from other portions of the assembly, and the radiation delivered to the selected portion is optimally delivered to the selected portion. Within the radiation range,
A method of sterilizing a stent delivery assembly, wherein the radiation is modified by passing through the cover and by backscattering of radiation to selected portions .   The method of claim 1, wherein the cover increases or decreases the radiation delivered to the selected portion.   The method of claim 1, wherein the radiation is E-beam radiation.   The method of claim 1, wherein the selected portion comprises a stent. The method of claim 4 , wherein the cover includes a sheath or sleeve, and the sheath or sleeve is disposed along an outer periphery of the stent.   The cover includes a first side and a second side, the first side covers a side of a selected portion facing radiation coming from a radiation source, and the second side is radiation. The method of claim 1, wherein the method covers the side of a selected portion opposite the radiation coming from the source. The method of claim 6 , wherein the radiation is modified by passing through a first side and the radiation is modified by reflection from a second side.   2. The cover of claim 1, wherein the cover covers a side of a selected portion facing the radiation coming from the radiation source and the side of the selected portion opposite the radiation coming from the radiation source is free of the cover. Method.   The method of claim 1, wherein the material thickness and density are selected such that radiation delivered to the selected portion increases or decreases to an optimal delivery radiation range.   The method of claim 1, wherein an optimal delivery radiation range for the selected portion is 22 kGy to 27 kGy.   The method of claim 1, wherein the radiation from the radiation source is between 38 kGy and 42 kGy.   The method of claim 1, wherein the cover comprises a metal, a polymer, or a combination thereof. Exposing the stent delivery assembly encapsulated in a package to radiation from a radiation source, wherein the package selectively modifies the radiation from the radiation source delivered to the selected portion of the assembly. one or more of the modifier (modifier) part to only including,
A selected portion of the assembly has an optimal delivery radiation range that is different from other portions of the assembly, and the radiation delivered to the selected portion is optimally delivered to the selected portion. Within the radiation range,
A method of sterilizing a stent delivery assembly, wherein the radiation is modified by passing through the modifier portion and by backscattering of radiation to a selected portion . Wherein the radiation is E-beam radiation The method of claim 1 3. The selected portion of the assembly has an optimal delivery radiation range that is different from other portions of the assembly, and the radiation is modified by the modifier portion so that it is delivered to the selected portion. that the radiation is within the optimum delivery radiation range for the selected portion, the method according to claim 1 3. It said selected portion comprises a stent method according to claim 1 3. The package includes a flexible pouch, and one of the modifier portions is attached or coupled to the flexible pouch that selectively modifies the radiation from the radiation source. containing modifier, method of claim 1 3. The package includes a rigid box, and one of the modifier portions includes a modifier element attached to or coupled to the package that selectively modifies the radiation from the radiation source. the method of claim 1 3. The modifier one modifier section of the Ya portions, or is integral with the package, or is incorporated into the package, the method according to claim 1 3. Modifier moiety, wherein comprises a receptacle that is or incorporated is coupled into the package, a removable element is disposed in said insertion mouth for modifying the radiation, according to claim 1 3 the method of. A package comprising a stent delivery assembly and one or more modifier portions;
The assembly is disposed within the package and the one or more modifier portions modify the radiation delivered to a selected portion of the assembly when radiation is directed from the radiation source to the assembly. Positioned relative to the selected portion of the assembly ;
A selected portion of the assembly has an optimal delivery radiation range that is different from other portions of the assembly, and the radiation delivered to the selected portion is optimally delivered to the selected portion. Within the radiation range,
A system for sterilizing a stent delivery assembly with radiation, wherein the radiation is modified by passing through the modifier portion and by backscattering of radiation to a selected portion . A stent delivery assembly, and a cover covering selected portions of the assembly;
The cover modifies radiation delivered to the selected portion of the assembly when radiation is directed from the radiation source to the assembly ;
A selected portion of the assembly has an optimal delivery radiation range that is different from other portions of the assembly, and the radiation delivered to the selected portion is optimally delivered to the selected portion. Within the radiation range,
A system for sterilizing a stent delivery assembly using radiation, wherein the radiation is modified by passing through the cover and by backscattering of radiation to selected portions . Exposing the stent delivery assembly to radiation from a radiation source;
The assembly is disposed in a package supported by a fixture, and a modifier portion of the fixture selectively selects the radiation from the radiation source delivered to a selected portion of the assembly. Fix ,
A selected portion of the assembly has an optimal delivery radiation range that is different from other portions of the assembly, and the radiation delivered to the selected portion is optimally delivered to the selected portion. Within the radiation range,
A method of sterilizing a stent delivery assembly, wherein the radiation is modified by passing through the modifier portion and by backscattering of radiation to a selected portion . 24. The method of claim 23 , wherein the modifier portion comprises a material that reflects radiation to a greater extent than other portions of the fixture. 24. The method of claim 23 , wherein the modifier portion comprises a material that reflects radiation to a lesser extent than other portions of the fixture.

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